Bacterial infection is linked to the etiology of periodontal diseaes; however, the role of miroorganisms in the pathogenesis of these disorders is not clear. One proposed mechanism by which suspected periodontopathogens may act to cause disease is the impairment of host defenses. In this regard, we have domonstrated the presence of non-cytotoxic immunosuppressive factors in the soluble sonic extracts of several strains of Actinobacillus actinomycetemcomitans, Treponema denticola and Fusobacterium nucleatum. Based on both our findings and evidence from several clinical studies, we propose that immune dysfunction may play a role in the etiology of periodontal disease and be linked to the immunosuppressive ability of periodontopathogens. The specific aims of this proposal are: 1) to evaluate suspected periodontopathogens for their ability to inhibit lymphocyte responses; 2) to fully characterize these inhibitory factors for their ability to alter T-cell and monocyte/macrophage function; 3) to purify and physiochemically characterize these bacterial agents; 4) to determine the mode of action of these immunosupressive factors; and 5) to test the inhibitory factors for their ability to depress immune function in vivo. For these studies, human peripheral blood lymphocytes will be utilized in a series of in vitro assays in order to asess sevral parameters of immune function. The factors will also be administered to rats either IV, IP or ID in order to assess effects on in vivo parameters of immune function (both cell mediated and humoral immunity). The fundamental hypothesis to be tested is that certain plaque associated bacteria may produce factors that cause immunosuppression the effects of which might be to enhance their own pathogenicity or that of other opportunistic organisms. It is anticipated that these studies will provide a basis for future clinical investigations that could directly implicate such suppressive factors in the pathogenesis of periodontal disease. Furthermore, these studies may provide a rationale and basis for the early detection and prevention of disease as well as for alternative approaches to therapeutic intervention and management of these patients.